Active Cortical Networks Research Articles

Parallelized Mechanical Stimulation of Neuronal Calcium Through Cell-Internal Nanomagnetic Forces Provokes Lasting Shifts in the Network Activity State.

Neurons differentiate mechanical stimuli force and rate to elicit unique functional responses, driving the need for further tools to generate various mechanical stimuli. Here, cell-internal nanomagnetic forces (iNMF) are introduced by manipulating internalized magnetic nanoparticles with an external magnetic field across cortical neuron networks in vitro. Under iNMF, cortical neurons exhibit calcium (Ca2+) influx, leading to modulation of activity observed through Ca2+ event rates. Inhibiting particle uptake or altering nanoparticle exposure time reduced the neuronal response to nanomagnetic forces, exposing the requirement of nanoparticle uptake to induce the Ca2+ response. In highly active cortical networks, iNMF robustly modulates synchronous network activity, which is lasting and repeatable. Using pharmacological blockers, it is shown that iNMF activates mechanosensitive ion channels to induce the Ca2+ influx. Then, in contrast to transient mechanically evoked neuronal activity, iNMFactivates Ca2+-activated potassium (KCa) channelsto stabilize the neuronal membrane potential and induce network activity shifts. The findings reveal the potential of magnetic nanoparticle-mediated mechanical stimulation to modulate neuronal circuit dynamics, providing insights into the biophysics of neuronal computation.

Active cortical networks promote shunting fast synaptic inhibition in vivo

Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABAARs). Despite their fundamental role, it is still not known how GABAARs signal in the intact brain. Here, we use invivo gramicidin recordings to investigate synaptic GABAAR signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients. In anesthetized cortex, synaptic GABAARs exert classic hyperpolarizing effects. In contrast, GABAAR-mediated synaptic signaling in awake cortex is found to be predominantly shunting. This is due to more depolarized GABAAR equilibrium potentials (EGABAAR), which are shown to result from the high levels of synaptic activity that characterize awake cortical networks. Synaptic EGABAAR observed in awake cortex facilitates the desynchronizing effects of inhibitory inputs upon local networks, which increases the flexibility of spiking responses to external inputs. Our findings therefore suggest that GABAAR signaling adapts to optimize cortical functions.

Lying and the Subsequent Desire for Toothpaste: Activity in the Somatosensory Cortex Predicts Embodiment of the Moral-Purity Metaphor

It is well known from literature and religious ceremonies that there is a link between physical cleansing and moral transgressions. Only recently, psychological experiments explored this association and demonstrated that a threat to moral purity increases the demand of physical cleansing. Moreover, it has been shown that physical cleansing is actually efficacious to cope with threatened morality. This so-called Macbeth effect has been explained by an embodiment of the moral-purity metaphor. We tested this hypothesis by means of an functional magnetic resonsce imaging (fMRI) experiment. Participants were instructed to enact scenarios including either an immoral act (lying) or a moral deed (telling the truth). Subsequently, the participants were asked to rate the desirableness of various products. Results revealed that participants rated cleansing products (but not other goods) more desirable after performing an immoral than after a moral act. This Macbeth effect was accompanied by an active cortical network including sensorimotor brain areas during rating of cleansing products (but not while evaluating noncleansing goods). The results demonstrate neurobiological evidence for an embodiment of the moral-purity metaphor. Thus, abstract thoughts about morality can be grounded in sensory experiences.

Endogenous and exogenous electric fields as modifiers of brain activity: rational design of noninvasive brain stimulation with transcranial alternating current stimulation

Synchronized neuronal activity in the cortex generates weak electric fields that are routinely measured in humans and animal models by electroencephalography and local field potential recordings. Traditionally, these endogenous electric fields have been considered to be an epiphenomenon of brain activity. Recent work has demonstrated that active cortical networks are surprisingly susceptible to weak perturbations of the membrane voltage of a large number of neurons by electric fields. Simultaneously, noninvasive brain stimulation with weak, exogenous electric fields (transcranial current stimulation, TCS) has undergone a renaissance due to the broad scope of its possible applications in modulating brain activity for cognitive enhancement and treatment of brain disorders. This review aims to interface the recent developments in the study of both endogenous and exogenous electric fields, with a particular focus on rhythmic stimulation for the modulation of cortical oscillations. The main goal is to provide a starting point for the use of rational design for the development of novel mechanism-based TCS therapeutics based on transcranial alternating current stimulation, for the treatment of psychiatric illnesses.

Neocortical Somatostatin-Expressing GABAergic Interneurons Disinhibit the Thalamorecipient Layer 4

Subtypes of GABAergic interneurons (INs) are crucial for cortical function, yet their specific roles are largely unknown. In contrast to supra- and infragranular layers, where most somatostatin-expressing (SOM) INs are layer 1-targeting Martinotti cells, the axons of SOM INs in layer 4 of somatosensory cortex largely remain within layer 4. Moreover, we found that whereas layers 2/3 SOM INs target mainly pyramidal cells (PCs), layer 4 SOM INs target mainly fast-spiking (FS) INs. Accordingly, optogenetic inhibition of SOM INs in an active cortical network increases the firing of layers 2/3 PCs whereas it decreases the firing of layer 4 principal neurons (PNs). This unexpected effect of SOM INs on layer 4 PNs occurs via their inhibition of local FS INs. These results reveal a disinhibitory microcircuit in the thalamorecipient layer through interactions among subtypes of INs and suggest that the SOM IN-mediated disinhibition represents an important circuit mechanism for cortical information processing.

Transient reduction of spontaneous neuronal network activity by sublethal amyloid β (1–42) peptide concentrations

Soluble amyloid beta(1-42) (A beta(1-42)) peptide has recently been assigned a key role in early Alzheimer's disease (AD) pathophysiology accounting for synaptic dysfunction before amyloid plaque formation and neurodegeneration can occur. Following sublethal A beta(1-42) administration, we observed an acute but transient reduction of the spike and burst rate of spontaneously active cortical networks cultured on microelectrode arrays. This simple experimental system appears suitable for future long-term pharmacological and genetic studies of A beta(1-42) signaling, thus providing a valuable new tool in AD research.

Synaptic Transmission and Plasticity in an Active Cortical Network

BackgroundThe cerebral cortex is permanently active during both awake and sleep states. This ongoing cortical activity has an impact on synaptic transmission and short-term plasticity. An activity pattern generated by the cortical network is a slow rhythmic activity that alternates up (active) and down (silent) states, a pattern occurring during slow wave sleep, anesthesia and even in vitro. Here we have studied 1) how network activity affects short term synaptic plasticity and, 2) how synaptic transmission varies in up versus down states.Methodology/Principal FindingsIntracellular recordings obtained from cortex in vitro and in vivo were used to record synaptic potentials, while presynaptic activation was achieved either with electrical or natural stimulation. Repetitive activation of layer 4 to layer 2/3 synaptic connections from ferret visual cortex slices displayed synaptic augmentation that was larger and longer lasting in active than in silent slices. Paired-pulse facilitation was also significantly larger in an active network and it persisted for longer intervals (up to 200 ms) than in silent slices. Intracortical synaptic potentials occurring during up states in vitro increased their amplitude while paired-pulse facilitation disappeared. Both intracortical and thalamocortical synaptic potentials were also significantly larger in up than in down states in the cat visual cortex in vivo. These enhanced synaptic potentials did not further facilitate when pairs of stimuli were given, thus paired-pulse facilitation during up states in vivo was virtually absent. Visually induced synaptic responses displayed larger amplitudes when occurring during up versus down states. This was further tested in rat barrel cortex, where a sensory activated synaptic potential was also larger in up states.Conclusions/SignificanceThese results imply that synaptic transmission in an active cortical network is more secure and efficient due to larger amplitude of synaptic potentials and lesser short term plasticity.

Thinking on luxury or pragmatic brand products: Brain responses to different categories of culturally based brands

Culturally based brands have a high impact on people's economic actions. Here we aimed to examine whether socioeconomic information conveyed by certain classes of brands (prestigious versus pragmatic classes) differentially evoke brain response. We presented icons of brands while recording subject's brain activity during a functional magnetic resonance imaging (fMRI) session. After the experiment, we asked subjects to assess the brands according to different characteristics. Results revealed an active network of bilateral superior frontal gyri, hippocampus and posterior cingulate related to familiar brands in general. Brands of the category sports and luxury activated regions in medial prefrontal cortex (MPFC) and precuneus. In contrast, brands rated as value products activated the left superior frontal gyrus and anterior cingulate cortex (ACC). The results suggest an active cortical network related to cognitive control for value brands and a network known to be associated with self-relevant processing for prestigious brands. We discuss the results as differential engagement of the prefrontal cortex depending on the attributed characteristic of a brand.

Impact of Cortical Network Activity on Short-term Synaptic Depression

Repetitive stimulation of synaptic connections in the cerebral cortex often induces short-term synaptic depression (STD), a property directly related to the probability of transmitter release and critical for the computational properties of the network. In order to explore how spontaneous activity in the network affects this property, we first studied STD in cortical slices that were either silent or that displayed spontaneous rhythmic slow oscillations resembling those recorded during slow wave sleep in vivo. STD was considerably reduced by the occurrence of spontaneous rhythmic activity in the cortical network. Once the rhythmic activity started, depression decreased over time in parallel with the duration and intensity of the ongoing activity until a plateau was reached. Thalamocortical and intracortical synaptic potentials studied in vivo also showed stronger depression in a silent than in an active cortical network, and the depression values in the active cortical network in vivo were indistinguishable from those found in active slices in vitro. We suggest that this phenomenon is due to the different steady states of the synapses in active and in silent networks.

Inhibitory Postsynaptic Potentials Carry Synchronized Frequency Information in Active Cortical Networks

Temporal precision in spike timing is important in cortical function, interactions, and plasticity. We found that, during periods of recurrent network activity (UP states), cortical pyramidal cells in vivo and in vitro receive strong barrages of both excitatory and inhibitory postsynaptic potentials, with the inhibitory potentials showing much higher power at all frequencies above approximately 10 Hz and more synchrony between nearby neurons. Fast-spiking inhibitory interneurons discharged strongly in relation to higher-frequency oscillations in the field potential in vivo and possess membrane, synaptic, and action potential properties that are advantageous for transmission of higher-frequency activity. Intracellular injection of synaptic conductances having the characteristics of the recorded EPSPs and IPSPs reveal that IPSPs are important in controlling the timing and probability of action potential generation in pyramidal cells. Our results support the hypothesis that inhibitory networks are largely responsible for the dissemination of higher-frequency activity in cortex.

FMRI reveals large-scale network activation in minimally conscious patients

The minimally conscious state (MCS) resulting from severe brain damage refers to a subset of patients who demonstrate unequivocal, but intermittent, behavioral evidence of awareness of self or their environment. Although clinical examination may suggest residual cognitive function, neurobiological correlates of putative cognition in MCS have not been demonstrated. To test the hypothesis that MCS patients retain active cerebral networks that underlie cognitive function even though command following and communication abilities are inconsistent. fMRI was employed to investigate cortical responses to passive language and tactile stimulation in two male adults with severe brain injuries leading to MCS and in seven healthy volunteers. In the case of the patient language-related tasks, auditory stimulation with personalized narratives elicited cortical activity in the superior and middle temporal gyrus. The healthy volunteers imaged during comparable passive language stimulation demonstrated responses similar to the patients' responses. However, when the narratives were presented as a time-reversed signal, and therefore without linguistic content, the MCS patients demonstrated markedly reduced responses as compared with volunteer subjects, suggesting reduced engagement for "linguistically" meaningless stimuli. The first fMRI maps of cortical activity associated with language processing and tactile stimulation of patients in the minimally conscious state (MCS) are presented. These findings of active cortical networks that serve language functions suggest that some MCS patients may retain widely distributed cortical systems with potential for cognitive and sensory function despite their inability to follow simple instructions or communicate reliably.

Contribution of intrinsic and synaptic factors in the desynchronization of thalamic oscillatory activity

The interplay between the intrinsic properties of thalamocortical (TC) neurons and synaptic potentials was investigated in vivo, in decorticated and intact-cortex cats, as well as in computational models to elucidate the possible mechanisms underlying the disruption of the spindle oscillation, a network phenomenon. We found that the low-threshold spikes (LTSs) in TC neurons were graded in their amplitude and latency to peak when elicited by current pulses or synaptic potentials from physiological levels of hyperpolarization. IPSPs could either delay or shunt the LTSs. Although the onset of spindles was rhythmic and did not include rebound LTSs, the end of spindles was highly aperiodic suggesting that desynchronization could contribute to the spindle termination. The desynchronization could have several sources, the main of which are (a) intrinsically generated rebound LTSs in TC neurons that occur with different delays and keep thalamic reticular (RE) neurons relatively depolarized, and/or (b) out-of-phase firing of cortical neurons due to intracortical processes that would result in depolarization of both TC and RE neurons. The present study suggests that an active cortical network participates in disrupting the spindle activities. We propose that the progression of spindles contains at least three different phases, with different origins: (a) the onset is generated by RE neurons that impose their activity onto TC neurons, without participation of cortical neurons; (b) the middle part is produced by the interplay between RE and TC neurons, with potentiation from the cortical network; and (c) the waning of spindles is due to the out-of-phase firing of TC and particularly cortical neurons that participate in the spindle termination.

Contribution of intrinsic and synaptic factors in the desynchronization of thalamic oscillatory activity

The interplay between the intrinsic properties of thalamocortical (TC) neurons and synaptic potentials was investigated in vivo, in decorticated and intact-cortex cats, as well as in computational models to elucidate the possible mechanisms underlying the disruption of the spindle oscillation, a network phenomenon. We found that the low-threshold spikes (LTSs) in TC neurons were graded in their amplitude and latency to peak when elicited by current pulses or synaptic potentials from physiological levels of hyperpolarization. IPSPs could either delay or shunt the LTSs. Although the onset of spindles was rhythmic and did not include rebound LTSs, the end of spindles was highly aperiodic suggesting that desynchronization could contribute to the spindle termination. The desynchronization could have several sources, the main of which are (a) intrinsically generated rebound LTSs in TC neurons that occur with different delays and keep thalamic reticular (RE) neurons relatively depolarized, and/or (b) out-of-phase firing of cortical neurons due to intracortical processes that would result in depolarization of both TC and RE neurons. The present study suggests that an active cortical network participates in disrupting the spindle activities. We propose that the progression of spindles contains at least three different phases, with different origins: (a) the onset is generated by RE neurons that impose their activity onto TC neurons, without participation of cortical neurons; (b) the middle part is produced by the interplay between RE and TC neurons, with potentiation from the cortical network; and (c) the waning of spindles is due to the out-of-phase firing of TC and particularly cortical neurons that participate in the spindle termination.